Hexamethylenetetramine n bismuth iodide



UNITED STATES PATENT- OFFICE HEXAMETHYLENETETRAMINE N BISMUTH IODIDE Oscar George Salb, Seymour, Ind., assignor to Salb Laboratories, Inc., Indianapolis, Ind., a corporation of Indiana No Drawing. Application June 13,1932, Serial No. 617,057 r 8 Claims. (01. 260437) This invention relates to the manufacture of the crystalline compound formed may be carried hexamethylenetetramine N bismuth iodide which on until a compound of the desired theoretical has valuable therapeutic properties. formula is obtained.

An object of the present invention is to provide More specifically, and by way of example, the {5. an organo-bismuth compound which may be adcompound may be prepared by dissolving 58.9 ministered orally for efiectively treating venereal parts by weight of purified. bismuth triiodide, in diseases, especially syphilis. Another object is to about 195 to 200 parts by weight of absolute alprovide a process of preparing such compound cohol. To the alcohol is previously added in pure form suitable for therapeutic use. parts by weight of freshly distilled hydriodic acid 1Q Heretofore, active treatment of syphilis was which is free from uncombined iodine. 10 generally performed by intramuscular and intra- To the resulting solution, which is heated and venous injections when metal compounds, inkept boiling, is added a solution containing 14.0 cluding those of bismuth, were used. The comparts by weight of hexamethylene tetramine dispound of the present invention comprises an solved in 115 to 120 parts by weight of absolute iodo-bismuth derivative of hexamethylene tetraalcohol. This solution is boiled and added very 15 mine which may be given by mouth in capsule or gradually withconstant stirring to the solution of tablet form, with the same effect as that obtained bismuth tri odide Wh le he a te s k p at 0 by injection of other well known compounds, and ing temperature. A copious dark red precipitate in some cases, withmore rapid beneficial results. forms which is allowed. to stand i t e p For therapeutic purposes, the metallic content natant liquid for several hours after which the 20 of a given compound is of the utmost importance. precipitate s s p a y filtration Otherwise To prevent kidney destruction, the metal content and dried at below 100C. should not be greater than that which can be The formula ofthe preferred form of my comsafely taken care of by the kidneys. Bismuth is pound m y be r p e nted graph c lly y present in the preferred form of my compound to 3 4 2 6 d s a y y e f0110Wing1 25 the extent of 27% by weight and in some cases N less, as found by chemical analysis. The bismuth exists as an anion and because of this fact, it more readily penetrates the chloroid plexus. 7 H CH2 CH? 3 0 Nitrogen is present to the extent of 7.42% and 30 iodine to the extent of 51.50%, as found by analy- N sis. The bismuth is attached directly to nitrogen l in the compound in which respect it is similar to protein derivatives. Ordinarily when heavy me-t N N-Bin als are attached to a carbon group, it is impossible 35 to disassociate the groups or group endings.

Iodine, although it has no definite bactericidal 0H1 effect, has the effect of hastening absorption and Theoretically this compound contains 28.54% excretion. bismuth, 52.24% iodine, and 7.68% nitrogen. In general, a compound of the present inven- This compound is a bright red crystalline sub- 40 tion may be prepared in pure form by producing stance insoluble in water, fats, oils, benzene, albismuth chloride and reacting this with prefercohol, ether, chloroform, carbon disulphide, but is ably freshly distilled hydriodic acid free from unslightly soluble in acetone and xylol. On heating combined iodine. The concentration of the hydrithe compound above 100 C'., it turns very dark odic acid should be 30%. Bismuth thiiodide is and on cooling, it assumes its original color. 45 thus formed. This may be purified by crystal- Above 100 C. the compound decomposes with lization and then dissolved in absolute alcohol liberation of iodine. which should preferably contain hydriodicacid. By varying the proportions of the hydriodic The resulting solutionis reacted with hexamethylacid and the hexamethylenetetramine in the enetetramine (otherwise known as formin or above procedure, it is possible to produce a com- 50 hexamine) preferably dissolved in absolute alcopound containing varying percentages of bishol. The mixture is thoroughly boiled wheremuth, and of iodine. For instance, by using an upon a red copious crystalline precipitate forms, excess of hydriodic acid, I can produce a comand the reacting materials are permitted to stand pound that has a much higher iodine content but until the reaction is complete. Purification of a lower bismuth content. In producing a com- 55 the administration of therapeutic doses can be,

demonstrated by quantitative chemical methods.

The above compound being insoluble in water, is admirably adapted for internal medication due to the fact that the bismuth is slowly liberated and does not cause kidney damage, as, would a' soluble salt of bismuth or other heavy metal. The protection given by bismuth as a preventive for syphilis, generally exceeds that conferred by other well known substances, and it may be par ticularly given in cases which are hypersensitive toward such other substances. Developments in the field may show that the compound hereinbefore described has utility in treating other diseases. V

What I claim is:

1. A process of preparing hexamethylenetetramine bismuth iodide, which process comprises reacting hexamethylenetetramine with bismuth iodide in the presence of hydriodic acid liquid solution the solvent in which permits the precipitation of hexamethylenetetramine bismuth iodide thus formed.

2. A process of preparing hexamethylenetetramine bismuth iodide, which process comprises dissolving bismuth iodide in alcohol containing hydriodic acid, and adding to the resulting solution a solution of hexamethylenetetramine in alcohol to form a precipitate comprising hexamethylenetetramine bismuth iodide.

3. A process of preparing hexamethylenetetramine bismuth iodide, which process comprises reacting bismuth chloride with hydriodic acid to form bismuth iodide, dissolving the resulting bismuth iodide in absolute alcohol containing hydriodic acid, and adding to the resulting solution hexamethylenetetramine to form a precipitate of hexamethylenetetramine bismuth iodide.

4. A process of preparing hexamethylenetetramine bismuth iodide for therapeutic use, which process comprises reacting bismuth chloride with a freshly distilled hydriodic acid product free from iodine and containing 30% hydriodic acid to form bismuth triiodide, purifying the bismuth .number of the usual organic solvents, and being a valuable anti-syphilitic for oral administration.

.6. In a process of preparing a compound for therapeutic use, reacting hexamethylenetetramine and bismuth iodide in the presence of hydriodic acid in a solvent that permits precipitation of hexamethylenetetramine bismuth iodide thus formed, separating the precipitate from the solvent and purifying the separated solid for therapeutic use.

'7. A process of preparing a compound for therapeutic use, which process comprises bringing together a solution of bismuth triiodide prepared by dissolving substantially 58.9 parts by weight of bismuth triiodide in about 195 to about 200 parts by weight of absolute alcohol to which has been added about 10 parts by weight of hydriodic acid; and a solution containing about 14 parts by weight of hexamethylenetetramine dissolved in about 115 to about 120 parts by weight of absolute alcohol; thereby forming a precipitate comprising hexamethylenetetramine bismuth iodide, and separating the precipitate from the resulting material to provide a product for oral administration in syphilis treatment.

8. A compound for therapeutic use having substantially the following formula:

the said compound being a valuable anti-syphilitic for oral administration.

OSCAR GEORGE SALE. 

